title: Ataxia with isolated vitamin E deficiency: heterogeneity of mutations and phenotypic variability in a large number of families.
abstract: Ataxia with vitamin E deficiency (AVED), or familial isolated vitamin E deficiency, is a rare autosomal recessive neurodegenerative disease characterized clinically by symptoms with often striking resemblance to those of Friedreich ataxia. We recently have demonstrated that AVED is caused by mutations in the gene for alpha-tocopherol transfer protein (alpha-TTP). We now have identified a total of 13 mutations in 27 families. Four mutations were found in >=2 independent families: 744delA, which is the major mutation in North Africa, and 513insTT, 486delT, and R134X, in families of European origin. Compilation of the clinical records of 43 patients with documented mutation in the alpha-TTP gene revealed differences from Friedreich ataxia: cardiomyopathy was found in only 19% of cases, whereas head titubation was found in 28% of cases and dystonia in an additional 13%. This study represents the largest group of patients and mutations reported for this often misdiagnosed disease and points to the need for an early differential diagnosis with Friedreich ataxia, in order to initiate therapeutic and prophylactic vitamin E supplementation before irreversible damage develops.
authors.affiliation: Institut de Genetique et de Biologie Moleculaire et Cellulaire, Centre National de la Recherche Scientifique/Institut Nationale de la Sante et de la Recherche Medicale/Universite Louis Pasteur, Strasbourg, France.
authors.forename: L
authors.initials: L
authors.lastname: Cavalier
authors.forename: K
authors.initials: K
authors.lastname: Ouahchi
authors.forename: H J
authors.initials: HJ
authors.lastname: Kayden
authors.forename: S
authors.initials: S
authors.lastname: Di Donato
authors.forename: L
authors.initials: L
authors.lastname: Reutenauer
authors.forename: J L
authors.initials: JL
authors.lastname: Mandel
authors.forename: M
authors.initials: M
authors.lastname: Koenig
mesh_terms: D000293:Adolescent; D000328:Adult; D000352:Africa, Northern; D017668:Age of Onset; D001259:Ataxia / Q000145:classification / Q000150:complications / Q000235:genetics*; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003937:Diagnosis, Differential; D005060:Europe; D005190:Family; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D017354:Point Mutation; D011401:Promoter Regions, Genetic; D017384:Sequence Deletion; D014811:Vitamin E Deficiency / Q000150:complications / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; C017763:alpha-tocopherol transfer protein